Interferons transcriptionally up-regulate MLKL expression in cancer cells

  • Interferons (IFNs) are key players in the tumor immune response and act by inducing the expression of IFN-stimulated genes (ISGs). Here, we identify the mixed-lineage kinase domain-like pseudokinase (MLKL) as an ISG in various cancer cell lines. Both type I and type II IFNs increase the expression of MLKL indicating that MLKL up-regulation is a general feature of IFN signaling. IFNγ up-regulates mRNA as well as protein levels of MLKL demonstrating that IFNγ transcriptionally regulates MLKL. This notion is further supported by Actinomycin D chase experiments showing that IFNγ-stimulated up-regulation of MLKL is prevented in the presence of the transcriptional inhibitor Actinomycin D. Also, knockdown of the transcription factor IFN-regulatory factor 1 (IRF1) and signal transducer and activator of transcription (STAT) 1 as well as knockout of IRF1 significantly attenuate IFNγ-mediated induction of MLKL mRNA levels. Up-regulation of MLKL by IFNγ provides a valuable tool to sensitize cells towards necroptotic cell death and to overcome apoptosis resistance of cancer cells.
Metadaten
Author:Anne-Kathrin Knuth, Stefanie Rösler, Barbara Schenk, Lisa Kowald, Sjoerd van Wijk, Simone FuldaORCiDGND
URN:urn:nbn:de:hebis:30:3-492031
DOI:https://doi.org/10.1016/j.neo.2018.11.002
ISSN:1522-8002
ISSN:1476-5586
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30521981
Parent Title (English):Neoplasia
Publisher:Stockton Press
Place of publication:Basingstoke
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/12/03
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/03/21
Volume:21
Issue:1
Page Number:8
First Page:74
Last Page:81
Note:
© 2018 Published by Elsevier Inc. on behalf of Neoplasia Press, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
HeBIS-PPN:448050161
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0